Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus.
Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity.


The effect of surface treatments on the adhesion of electrochemically deposited hydroxyapatite coating to titanium and on its interaction with cells and bacteria.
The effect of different mechanical and chemical pre-treatments on the adhesion strength of hydroxyapatite (HAp) coating on a commercially pure titanium (CP-Ti) substrate was studied by means of a standard tensile test followed by microscopic and chemical analysis to determine the locus of fracture. In addition, the effects of either these pre-treatments or post-treatment by low-energy electron irradiation, which allowed tuning the wettability of the surface, on both osteoblast progenitor attachment and S. aureus bacteria attachment were investigated. A dedicated program was developed for unambiguous identification and count of stained cells. A single-phase HAp coating was formed by electrodeposition. A series of surface pre-treatments consisted of grinding down to P1000, etching in HNO₃/HF solution, grit blast, soaking in NaOH and subsequent heat treatment provided the highest adhesion strength to the HAp coating. Osteoblast progenitors derived from rats may be attached preferentially to a hydrophilic surface (post-treatment to θ = 30°), while the bacteria seemed to be less attached to hydrophobic surfaces (post-treatment to θ = 105°). However, the results were not statistically different. The bacteria seemed to be less attached to the smoother, uncoated surfaces.


Differential modulation of Kv4 kinetics by KCHIP1 splice variants.
The beta-subunits of the KChIP family modulate properties and expression level of Kv4 channels. We report the cloning of the first splice variant of KChIP1 (KChIP1b) which contains an extra exon, rich in aromatic residues, in the amino terminus. Both splice variants interacted equally well with Kv4.2 subunits based on confocal imaging and upregulation of current density (more than five-fold). No effects on the voltage dependence of activation or inactivation were noted. However, the effects on the kinetics of recovery from inactivation were opposite: KChIP1b induced a slow component in the recovery (tau approximately 1.2 s), in contrast to the increased recovery rate (tau = 125 ms) with KChIP1a. Accordingly, frequency-dependent accumulation of inactivation was enhanced by KChIP1b but reduced by KChIP1a. Since Kv4.2 channels are involved in protection against back propagating action potentials in dendritic spines, a differential expression of either splice variant could shape the dendritic function.


Nitric oxide production and regulation of endothelial nitric-oxide synthase phosphorylation by prolonged treatment with troglitazone: evidence for involvement of peroxisome proliferator-activated receptor (PPAR) gamma-dependent and PPARgamma-independent signaling pathways.
Recently, peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been reported to increase endothelial NO, but the signaling mechanisms involved are unknown. Using troglitazone, a PPARgamma ligand known as an antidiabetic compound, we investigated the molecular mechanism of its effect on NO production in bovine aortic endothelial cells. Troglitazone increased endothelial NO production in a dose- and time-dependent manner with no alteration in endothelial nitric-oxide synthase (eNOS) expression. The maximal increase ( approximately 3.1-fold) was achieved with 20 microm troglitazone treatment for 12 h, and this increase was accompanied by increases in the expression of vascular endothelial growth factor (VEGF) and its receptor, KDR/Flk-1, and in Akt phosphorylation. Analysis with antibodies specific for each phosphorylated site demonstrated that troglitazone (20 microm treatment for 12 h) significantly increased both the phosphorylation of Ser(1179) of eNOS (eNOS-Ser(1179)) and the dephosphorylation of eNOS-Ser(116) but did not alter eNOS-Thr(497) phosphorylation. Treatment with anti-VEGF antibody to scavenge the increased VEGF induced by troglitazone partially inhibited troglitazone-stimulated NO production. This was accompanied by the attenuation of troglitazone-stimulated increases in the phosphorylation of Akt and eNOS-Ser(1179) with no alteration in eNOS-Ser(116) dephosphorylation. We also found that bisphenol A diglycidyl ether, a PPARgamma antagonist, partially inhibited troglitazone-stimulated NO production with a concomitant reduction in VEGF-KDR/Flk-1-Akt-mediated eNOS-Ser(1179) phosphorylation but with no alteration in eNOS-Ser(116) dephosphorylation induced by troglitazone. Taken together, our results demonstrate that prolonged treatment with troglitazone increases endothelial NO production by at least two independent signaling pathways: PPARgamma-dependent, VEGF-KDR/Flk-1-Akt-mediated eNOS-Ser(1179) phosphorylation and PPARgamma-independent, eNOS-Ser(116) dephosphorylation.


Tubular regeneration: when can the kidney regenerate from injury and what turns failure into success?
The most common intrarenal cause for acute kidney injury/renal failure is tubular damage. The kidney tubules are arranged as compartments of cellular mosaics to perform their functions, and at rest almost a fifth of the human ATP consumption is allotted to the reabsorption of substances from the filtrate, rendering especially the proximal tubules highly sensitive to oxygen and/or nutrient deprivation. Normally mitotically quiescent, the tubular epithelium shows a brisk regenerative response following injury if supportive care is offered, allowing functional restoration. Despite this, the cellular machinery behind the regenerative capacity is still not unequivocally defined. This is at odds with other epithelia such as those of the skin and intestine, where stem cells maintain a continuous flow of new cells from designated niches. This review discusses the classical concept of renal regeneration, i.e. stochastically surviving cells undergoing dedifferentiation (or epithelial-mesenchymal transition) followed by replenishment of the tubular epithelium. Furthermore however, this view has recently been challenged by the concept of organ-confined stem/progenitor cells, bone marrow-derived stem cells, or mesenchymal stem cells taking part in the regenerative events. Whereas results from animal models support the classical view, morphologically distinct cells have been demonstrated in human kidneys, requiring interpretation. This review presents some of the previous work and techniques and highlights issues that need to be reconciled. In adult humans, the kidney tubules contain scattered cells with a distinct set of markers and properties, such as increased robustness during tubular damage. These cells may be induced by injury or represent a resident progenitor cell pool. To date, animal studies using lineage-tracing methods argue for an inductive scenario. In humans, the situation is less clear and one might speculate that the cellular heterogeneity might reflect elements of cellular reprogramming to a progenitor-like state, perhaps by induction. Due to intense investigational efforts, however, a scientific consensus may soon be reached, which will benefit further research.


Brain stem evoked response audiometry in newborn hearing screening.
Brain stem evoked response audiometry (BERA) has been used as an auditory screening procedure in three groups of newborn infants. Group 1 consisted of 220 normal-term infants who were tested within 72 hours of birth; no hearing abnormalities were uncovered (386 ears), and their threshold responses (for clicks) lay between a 10- and 20-dB hearing level (re: adult). Group 2 consisted of 75 newborns who were treated in an intensive care unit for one to 14 weeks; four were found to have severe sensorineural hearing loss (seven ears) at the time of discharge. Group 3 consisted of a group of 325 infants, 1 year or older, who had previously been discharged from the same intensive care unit; of these infants, an additional four showed severe sensorineural hearing loss. All abnormalities that were identified by BERA were subsequently confirmed by conventional audiometric measures. The estimate of an incidence of severe hearing loss in one of 50 infants who required intensive care in the neonatal period calls for careful testing of this population.


Highly Stereocontrolled Ring-Opening Polymerization of Racemic Alkyl β-Malolactonates Mediated by Yttrium [Amino-alkoxy-bis(phenolate)] Complexes.
Yttrium [amino-alkoxy-bis(phenolate)]amido complexes have been used for the ring-opening polymerization (ROP) of racemic alkyl β-malolactonates (4-alkoxycarbonyl-2-oxetanones, rac-MLA(R) s) bearing an allyl (All), benzyl (Bz) or methyl (Me) lateral ester function. The nature of the ortho-substituent on the phenolate rings in the metal ancillary dictated the stereocontrol of the ROP, and consequently the syndiotactic enrichment of the resulting polyesters. ROP promoted by catalysts with halogen (Cl, Br)-disubstituted ligands allowed the first reported synthesis of highly syndiotactic PMLA(R) s (Pr ≥ 0.95); conversely, catalysts bearing bulky alkyl and aryl ortho-substituted ligands proved largely ineffective. All polymers have been characterized by (1) H and (13) C{(1) H} NMR spectroscopy, MALDI-ToF mass spectrometry and DSC analyses. Statistical and thermal analyses enabled the rationalization of the chain-end control mechanism. Whereas the stereocontrol of the polymerization obeyed a Markov first-order (Mk1) model for the ROP of rac-MLA(Bz) and rac-MLA(All) , the ROP of rac-MLA(Me) led to a chain end-control of Markov second-order type (Mk2). DFT computations suggest that the high stereocontrol ability featured by catalysts bearing Cl- and Br-substituted ligands does not likely originate from halogen bonding between the halogen substituent and the growing polyester chain.


Inapparent chlamydial infection in the urogenital tract of guinea-pigs.
Microbiologically inapparent urogenital infection appeared to be induced in male guinea-pigs inoculated intra-urethrally with low doses of the guinea-pig inclusion conjunctivitis strain (GP-IC) of Chlamydia psittaci. This state was indicated by the ability of inoculated animals to donate eye infection to normal animals caged with them. Donors failed to develop overt urogenital infection throughout the period of transmission judged by both absence of infected cells in urethral scrapings and failure to isolate GP-IC in cell culture; however, inoculation of donors with 5-iododeoxyuridine led to transient appearance of infectivity in scrapings. In distinction from overtly infected animals, donors failed to develop serum antibody and remained susceptible to urethral challenge with larger doses of GP-IC. Animals that had recovered from overt urethral infection were resistant to challenge and appeared unable to transmit eye infection.


Sequence homology between a beta-galactosidase and some beta-glucosidases.
A significant sequence homology was found between a thermostable beta-galactosidase from Sulfolobus solfataricus and two beta-glucosidases, respectively, from Caldocellum saccharolyticum and from Agrobacterium sp. These glycosidases appear to form a new protein family, since no homology could be detected with established beta-galactosidase or beta-glucosidase families.


Risk of mortality associated with respiratory syncytial virus and influenza infection in adults.
Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection. A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013-2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death. Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17-4.58). Oseltamivir had no significant effect on mortality in patients with influenza. RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.


A case of mosaic supernumerary ring chromosome 15 with two copies of the segment 15p11.1-q14.
Although supernumerary marker chromosomes derived from chromosome 15 (SMC(15)) are the most common marker chromosome in humans, ring SMC(15)s are rare. Here we report on a 16-month-old patient who has a ring SMC(15) with two copies of the segment 15p11.1-q14 region. She exhibits hypotonia, developmental delay, speech delay, microstomia, micrognathia, and other mild dysmorphic features. The ring was present in 22% of her peripheral blood lymphocyte cells. FISH study revealed that the ring was derived from chromosome 15, and had neither telomere sequence nor satellite III paracentromeric DNA. It had alpha satellite DNA, and two copies of the segment 15q11.2 to CTD 2125J1 (at 15q14, 2.2 Mbp telomeric of the common breakpoint 5). The ring-containing cells had four copies of 15p11.1-q14. The ring can be described as r(15)(::p11.1 --> q14::q14 --> p11.1::). Southern-blot analysis of the methylation pattern in the PW/AS critical region showed biparental inheritance, and the ring was maternally derived. This patient's phenotype was comparable to ring SMC(15) patients with three copies of the Prader-Willi/Angelman syndrome (PWS/AS) critical region.


[Chromosome variability in established cultures of Drosophila melanogaster embryonal cells].
Diploid cell lines with female karyotype for 7 years conserved the normal chromosome set. Tripoid and tetraploid chromosome sets also remained unchanged after two years of cultivation in both sublines. The karyotypes characterized by supernumerary X-chromosomes or deficient for one or more X-chromosomes are predominant among the aneuploids in diploid and euploid lines. The cloning technique allows to isolate the hyperploid variants only. The following karotypic changes were observed during prolonged cultivation: a loss of a single chromosome from the 4th pair; the X-autosome (third pair) translocation; the enlargement of a heterochromatic pricentromeric segment of the X-chromosome; the centric fusion of the X-chromosomes. The formation of 2 telocentric fragments as a result of the centromeric breakage of the autosome of the second pair is a typical chromosome aberration observed in diploid, triploid and tetraploid cell lines.


The C-terminal domain V of perlecan promotes beta1 integrin-mediated cell adhesion, binds heparin, nidogen and fibulin-2 and can be modified by glycosaminoglycans.
Domain V of the major basement-membrane proteoglycan perlecan, a domain which consists of three laminin type G (LG) and four epidermal-growth-factor-like (EG) modules, was obtained in recombinant form by transfecting embryonic kidney cells with an episomal expression vector. A major 90-kDa fragment V was obtained together with fragments Va (74 kDa) and Vb (26 kDa) which were generated by endogenous proteolysis in front of the most C-terminal LG module. All three fragments bound to a heparin affinity column and could be displaced at a moderate (0.2 M) NaCl concentration. Rotary-shadowing electron microscopy demonstrated a three-globule structure for fragment V. Fragment V also showed a strong immunological cross-reaction with tissue-derived perlecan, indicating that it was folded into a native structure. A further, larger fragment, Vc, was apparently substituted with heparan sulphate and/or chondroitin sulphate chains and failed to bind to heparin. Fragment V but not fragment Vc promoted a distinct adhesion of several cell lines and this could be blocked by antibodies against the integrin beta1 chain. This domain may, however, represent only one of several cell-adhesive sites of perlecan. The recombinant perlecan fragment V bound in surface plasmon resonance assays to fibulin-2, laminin-nidogen complex, nidogen and two nidogen fragments. This indicated two different nidogen-binding epitopes on perlecan domain V with about a 10-fold difference in their affinities (Kd = 0.05-0.2 microM and about 2 microM). Perlecan domain V therefore seems to participate in the supramolecular assembly and cell connections of basement membranes.


[Antigen-nonspecific suppression of the immune response in mice as affected by pertussis vaccine].
A study was made of the suppressorgenic action of killed whole-cell pertussis vaccine prepared from B. pertussis strains 475 and 305. Thymic and splenic lymphocytes of CBA mice 3-7 days following intraperitoneal or intravenous inoculation of pertussis vaccine were shown to inhibit in an antigen-nonspecific manner the plaque-forming cell (PFC) production in the adoptive transfer experiments. Suppression of graft-versus-host reaction was also observed, estimated by the survival of irradiated (CBA X C57BL/6) Fl mice, or by measuring the endogenous colony formation. Suppression-mediating cells were found to be susceptible to complement-dependent lysis by the anti-I-Jk alloantiserum against the specific marker of suppressor T cells, antigen I-J. Furthermore, thymocytes of pertussis vaccine-treated mice were shown to inhibit the endogenous colony formation in syngeneic mice irradiated in sublethal dose. Thus, B. pertussis vaccination of CBA mice resulted in appearance of suppressor T cells that exerted various inhibitory activities in several experimental test-systems.


Characterizing and modeling the dynamics of online popularity.
Online popularity has an enormous impact on opinions, culture, policy, and profits. We provide a quantitative, large scale, temporal analysis of the dynamics of online content popularity in two massive model systems: the Wikipedia and an entire country's Web space. We find that the dynamics of popularity are characterized by bursts, displaying characteristic features of critical systems such as fat-tailed distributions of magnitude and interevent time. We propose a minimal model combining the classic preferential popularity increase mechanism with the occurrence of random popularity shifts due to exogenous factors. The model recovers the critical features observed in the empirical analysis of the systems analyzed here, highlighting the key factors needed in the description of popularity dynamics.


Estrogen regulates the stage-specific expression of kidney androgen-regulated protein in rat uterus during reproductive cycle and pregnancy.
The female sex steroid, estrogen, acting through its nuclear receptor profoundly influences growth and differentiation programs in the mammalian uterus by regulating the expression of specific cellular genes. The identity and profile of expression of the estrogen-regulated genes at various stages of the reproductive cycle and pregnancy, however, remain largely unknown. Using a differential gene expression screen method, we isolated a gene that is down-regulated in the uterus during pregnancy. This gene encodes the previously identified androgen-regulated protein known as the kidney androgen-regulated protein (KAP) because of its abundant expression in the kidney. Our results showed a high level of KAP messenger RNA (mRNA) in the uteri of nonpregnant rats at all stages of the estrous cycle. We observed that in the pregnant animals, the level of KAP mRNA remained high immediately after fertilization (days 1 and 2), but declined sharply with the progression of pregnancy, falling to almost undetectable levels during midgestation (days 10-15). Interestingly, the level of KAP mRNA started to rise again toward the end (day 19 onward) of pregnancy and was high during parturition. The temporal pattern of expression of KAP in the uterus closely overlapped with the profile of plasma estrogen during pregnancy. Known antagonists of estrogen, such as tamoxifen and ICI 182,780, strongly inhibited uterine KAP gene expression during the estrous cycle and pregnancy, supporting a regulatory role of estrogen in this process. Consistent with this observation, administration of estrogen to ovariectomized animals markedly stimulated (approximately 10-fold) the level of KAP mRNA in the uterus. Treatment of these animals with progesterone, on the other hand, did not significantly after KAP gene expression. Immunocytochemical analyses of uterine sections with an antibody against KAP exhibited specific staining in both luminal and glandular epithelia and in myometrium. These uterine locations also possess abundant estrogen receptors and are known targets of estrogen action. Our studies, therefore, revealed that KAP is a useful marker of estrogen action in the uterus, especially during the reproductive cycle and termination of gestation.


RIL, a LIM gene on 5q31, is silenced by methylation in cancer and sensitizes cancer cells to apoptosis.
Gene silencing associated with promoter methylation can inactivate tumor suppressor genes (TSG) in cancer. We identified RIL, a LIM domain gene mapping to 5q31, a region frequently deleted in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), as methylated in 55 of 79 (70%) of cancer cell lines tested. In a variety of primary tumors, we found RIL methylation in 55 of 92 (60%) cases, with highest methylation in AML and colon cancer, and in 30 of 83 (36%) MDS samples, whereas normal tissues showed either absence or substantially lower levels of methylation, which correlates with age. RIL is ubiquitously expressed but silenced in methylated cancers and could be reactivated by the hypomethylating agent 5-aza-2'-deoxycytidine. Restoring RIL expression in colon cancer cells by stable transfection resulted in reduced cell growth and clonogenicity and an approximately 2.0-fold increase in apoptosis following UV exposure. In MDS, RIL methylation is a marker of adverse prognosis independent of chromosome 5 and 7 deletions. Our data suggest that RIL is a good candidate TSG silenced by hypermethylation in cancer.


Dementia with Lewy bodies.
Dementia with Lewy bodies (DLB) is the recommended term for a common cause of dementia characterized by the histological presence of distinctive inclusions within neurons, Lewy bodies (McKeith et al, 1996). Following increasing pathological recognition, core clinical diagnostic features have been identified to allow diagnosis in life. Insights into the biology of this type of neurodegeneration suggest that the regional patterns of involvement might allow therapeutic intervention. Although Lewy bodies had long been recognized in the substantia nigra and other subcortical nuclei in patients with Parkinson's disease (PD), it was only in the 1970s that a significant number of reports began to be published from Japan describing patients with dementia and parkinsonism associated with the presence of Lewy bodies in cortical neurons (reviewed by Kosaka, 1990). Since these reports, different workers have used a variety of terms to describe this disease process, including diffuse Lewy body disease (Yoshimura, 1983), Lewy body dementia (Gibb et al, 1987), senile dementia of Lewy body type (Perry et al, 1990a) and the Lewy body variant of Alzheimer's disease (Hansen et al, 1990).


Interaction of antiparallel microtubules in the phragmoplast is mediated by the microtubule-associated protein MAP65-3 in Arabidopsis.
In plant cells, microtubules (MTs) in the cytokinetic apparatus phragmoplast exhibit an antiparallel array and transport Golgi-derived vesicles toward MT plus ends located at or near the division site. By transmission electron microscopy, we observed that certain antiparallel phragmoplast MTs overlapped and were bridged by electron-dense materials in Arabidopsis thaliana. Robust MT polymerization, reported by fluorescently tagged End Binding1c (EB1c), took place in the phragmoplast midline. The engagement of antiparallel MTs in the central spindle and phragmoplast was largely abolished in mutant cells lacking the MT-associated protein, MAP65-3. We found that endogenous MAP65-3 was selectively detected on the middle segments of the central spindle MTs at late anaphase. When MTs exhibited a bipolar appearance with their plus ends placed in the middle, MAP65-3 exclusively decorated the phragmoplast midline. A bacterially expressed MAP65-3 protein was able to establish the interdigitation of MTs in vitro. MAP65-3 interacted with antiparallel microtubules before motor Kinesin-12 did during the establishment of the phragmoplast MT array. Thus, MAP65-3 selectively cross-linked interdigitating MTs (IMTs) to allow antiparallel MTs to be closely engaged in the phragmoplast. Although the presence of IMTs was not essential for vesicle trafficking, they were required for the phragmoplast-specific motors Kinesin-12 and Phragmoplast-Associated Kinesin-Related Protein2 to interact with MT plus ends. In conclusion, we suggest that the phragmoplast contains IMTs and highly dynamic noninterdigitating MTs, which work in concert to bring about cytokinesis in plant cells.


Distorted wave front produced by a high-resolution projection optical system having rotationally symmetric birefringence.
The influence of birefringence caused by rotationally symmetric stress distribution in a high-resolution projection optical system is investigated. The general form of the pupil function is derived based on the Jones matrix calculation, expressing the wave front as a combination of the two orthogonal polarization components. Assuming a linearly polarized incident beam, it is found that the main polarization portion of the wave front exiting the projection lens has astigmatic aberration in the Seidel region and shows phase singularity at four pupil points at which the amplitude transmittance becomes zero.


Sharing and reusing cell image data.
The rapid growth in content and complexity of cell image data creates an opportunity for synergy between experimental and computational scientists. Sharing microscopy data enables computational scientists to develop algorithms and tools for data analysis, integration, and mining. These tools can be applied by experimentalists to promote hypothesis-generation and discovery. We are now at the dawn of this revolution: infrastructure is being developed for data standardization, deposition, sharing, and analysis; some journals and funding agencies mandate data deposition; data journals publish high-content microscopy data sets; quantification becomes standard in scientific publications; new analytic tools are being developed and dispatched to the community; and huge data sets are being generated by individual labs and philanthropic initiatives. In this Perspective, I reflect on sharing and reusing cell image data and the opportunities that will come along with it.


Differential glycosaminoglycan binding of Chlamydia trachomatis OmcB protein from serovars E and LGV.
We recently showed that OmcB protein from Chlamydia trachomatis serovar LGV1 functions as an adhesin. In this study, we produced Escherichia coli expressing OmcB from serovar E and compared this OmcB to OmcB from serovar LGV1. Infectivity inhibition assays carried out with serovars LGV1 and E of C. trachomatis in the presence of recombinant OmcB showed considerable (approximately 60%) inhibition of infectivity. In the presence of heparan sulphate, there was significant inhibition (68%) of adherence of E. coli expressing OmcB from serovar LGV1 only. In a further experiment, recombinant OmcB from serovar LGV1 showed minimal binding to glycosaminoglycan (GAG)-deficient cells, whilst to the same cells, recombinant OmcB from serovar E showed binding equal to that to the wild-type cells. Our experiments strongly suggest that OmcB from serovar E, in contrast to that from serovar LGV1, is not binding to host cells through a GAG-dependent mechanism.


Phase-constrained parallel MR image reconstruction.
A generalized method for phase-constrained parallel MR image reconstruction is presented that combines and extends the concepts of partial-Fourier reconstruction and parallel imaging. It provides a framework for reconstructing images employing either or both techniques and for comparing image quality achieved by varying k-space sampling schemes. The method can be used as a parallel image reconstruction with a partial-Fourier reconstruction built in. It can also be used with trajectories not readily handled by straightforward combinations of partial-Fourier and SENSE-like parallel reconstructions, including variable-density, and non-Cartesian trajectories. The phase constraint specifies a better-conditioned inverse problem compared to unconstrained parallel MR reconstruction alone. This phase-constrained parallel MRI reconstruction offers a one-step alternative to the standard combination of homodyne and SENSE reconstructions with the added benefit of flexibility of sampling trajectory. The theory of the phase-constrained approach is outlined, and its calibration requirements and limitations are discussed. Simulations, phantom experiments, and in vivo experiments are presented.


A new modified forked flap with subcutaneous pedicles for adult cases of bilateral cleft lip nasal deformity: from normalization to aesthetic improvement.
In adult cases of bilateral cleft lip nasal deformity, an esthetically satisfying result can not be obtained only by manipulation inside the nose with the nasal tip pointing upward. The nasal tip should be made in a more anterior direction for nasal esthetic improvement. Additional tissue beyond the nose is needed, and the forked flap is a useful method in such cases. However, the blood circulation of long and narrow flaps containing the scar, especially after open rhinoplasty, is unstable. We have developed a new long and narrow forked flap that has a more stable blood circulation. The forked flap was made using two subcutaneous pedicles attached to the periphery of the each flap. We applied this flap to five adult cases of bilateral cleft lip nasal deformity. Four of the cases had the scar associated with the flying bird incision, and one case required no treatment after the primary repair. All the flaps took without signs of partial necrosis. In all cases, the nasal tip was projected forward with adequate columella elongation, and the profile was esthetically improved. In the final stage of correction for adult cases of bilateral cleft lip nasal deformity, this method, making maximum use of the tissue containing the scar in not only the white lip but also the vermilion, is very effective. It is very important to obtain nasal esthetic improvement for the adult patient with bilateral cleft lip nasal deformity.


Efficient markerless gene replacement in Corynebacterium glutamicum using a new temperature-sensitive plasmid.
Random chemical mutation of a Corynebacterium glutamicum-Escherichia coli shuttle vector derived from plasmid pCGR2 was done using hydroxylamine. It brought about amino acid substitutions G109D and E180K within the replicase superfamily domain of the plasmid's RepA protein and rendered the plasmid highly unstable, especially at higher incubation temperatures. Colony formation of C. glutamicum was consequently completely inhibited at 37°C but not at 25°C. G109 is a semi-conserved residue mutation which resulted in major temperature sensitivity. E180 on the other hand is not conserved even among RepA proteins of closely related C. glutamicum pCG1 family plasmids and its independent mutation caused relatively moderate plasmid instability. Nonetheless, simultaneous mutation of both residues was required to achieve temperature-sensitive colony formation. This new pCGR2-derived temperature-sensitive plasmid enabled highly efficient chromosomal integration in a variety of C. glutamicum wild-type strains, proving its usefulness in gene disruption studies. Based on this, an efficient markerless gene replacement system was demonstrated using a selection system incorporating the temperature-sensitive replicon and Bacillus subtilis sacB selection marker, a system hitherto not used in this bacterium. Single-crossover integrants were accurately selected by temperature-dependent manner and 93% of the colonies obtained by the subsequent sucrose selection were successful double-crossover recombinants.


Rapid 3D fluorescence imaging of individual optically trapped living immune cells.
We demonstrate an approach to rapidly characterize living suspension cells in 4 dimensions while they are immobilized and manipulated within optical traps. A single, high numerical aperture objective lens is used to separate the imaging plane from the trapping plane. This facilitates full control over the position and orientation of multiple trapped cells using a spatial light modulator, including directed motion and object rotation, while also allowing rapid 4D imaging. This system is particularly useful in the handling and investigation of the behavior of non-adherent immune cells. We demonstrate these capabilities by imaging and manipulating living, fluorescently stained Jurkat T cells.


Comparative assessment of software for non-targeted data analysis in the study of volatile fingerprint changes during storage of a strawberry beverage.
Five free software packages were compared to assess their utility for the non-targeted study of changes in the volatile profile during the storage of a novel strawberry beverage. AMDIS coupled to Gavin software turned out to be easy to use, required the minimum handling for subsequent data treatment and its results were the most similar to those obtained by manual integration. However, AMDIS coupled to SpectConnect software provided more information for the study of volatile profile changes during the storage of strawberry beverage. During storage, volatile profile changed producing the differentiation among the strawberry beverage stored at different temperatures, and this difference increases as time passes; these results were also supported by PCA. As expected, it seems that cold temperature is the best way of preservation for this product during long time storage. Variable Importance in the Projection (VIP) and correlation scores pointed out four volatile compounds as potential markers for shelf-life of our strawberry beverage: 2-phenylethyl acetate, decanoic acid, γ-decalactone and furfural.


Screening for Urinary Incontinence in Women: A Systematic Review for the Women's Preventive Services Initiative.
Urinary incontinence is infrequently addressed during routine health care despite its high prevalence and adverse effects on health. To evaluate whether screening for urinary incontinence in women not previously diagnosed improves outcomes (symptoms, quality of life, and function) and to evaluate the accuracy of screening methods and potential harms of screening. English-language searches of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (1 January 1996 to 30 March 2018); ClinicalTrials.gov (April 2018); and reference lists of studies and reviews. Randomized trials, cohort studies, systematic reviews of studies that enrolled nonpregnant women without previously diagnosed urinary incontinence and compared clinical outcomes and adverse effects between women who were and were not screened, and diagnostic accuracy studies that reported performance measures of screening tests. Dual extraction and quality assessment of individual studies. No studies evaluated the overall effectiveness or harms of screening. Seventeen studies evaluated the diagnostic accuracy of 18 screening questionnaires against a clinical diagnosis or results of diagnostic tests. Of these, 14 poor-quality studies were based in referral clinics, enrolled only symptomatic women, or had other limitations. One good-quality and 2 fair-quality studies (evaluating 4 methods) enrolled women not recruited on the basis of symptoms. Areas under the receiver-operating characteristic curve for stress, urge, and any type of incontinence in these studies were 0.79, 0.88, and 0.88 for the Michigan Incontinence Symptom Index; 0.85, 0.83, and 0.87 for the Bladder Control Self-Assessment Questionnaire; and 0.68, 0.82, and 0.75 for the Overactive Bladder Awareness Tool. The Incontinence Screening Questionnaire had a sensitivity of 66% and specificity of 80% for any type of incontinence. Studies enrolled few participants, often from symptomatic referral populations; used various reference standards; and infrequently reported CIs. Evidence is insufficient on the overall effectiveness and harms of screening for urinary incontinence in women. Limited evidence in general populations suggests fairly high accuracy for some screening methods. Health Resources and Services Administration.


Left ventricular dimensions and function during right ventricular pressure overload.
The effects of right ventricular (RV) pressure overload on left ventricular (LV) function is controversial. Therefore, we examined LV dimensions and shortening after acute and chronic pulmonary artery (PA) constriction in six conscious dogs, preinstrumented with LV and RV catheters, an LV micromanometer, a PA inflatable cuff occluder, and ultrasonic crystals to measure an LV anteroposterior, a septal-lateral, and a free wall segment chord. Studies were performed before, immediately after, and 2, 4, and 6 wk after PA constriction. With acute cuff inflation, RV systolic- and end-diastolic pressures rose, but LV end-diastolic pressure fell. Both septal-lateral end-diastolic length and systolic shortening declined 4.1 +/- 0.7 mm and 5.9 +/- 2.3% respectively (P less than 0.01), whereas the anteroposterior and segment chords were unaffected. With chronic RV pressure overload septal-lateral shortening but not end-diastolic length returned to control levels. Also the first derivative of LV pressure (LV dP/dt) fell 540 +/- 164 mmHg/s by 6 wk compared with control, but this decline was reversed by volume expansion with dextran. We conclude that RV pressure overload displaces the septum toward the LV free wall; acutely this displacement is primarily at end diastole, but chronically it occurs at end systole as well, maintaining the septal contribution to LV ejection. Thus chronic RV pressure overload is associated with significant changes in LV diastolic shape but maintenance of normal LV function.


Co-expression of somatostatin receptor subtypes and estrogen receptor-α mRNAs by non-functioning pituitary adenomas in young patients.
The expression by non-functioning adenomas (NFoma) of somatostatin receptor (SSTR) subtypes and estrogen receptor (ERα) is poorly understood. Consequently, the mRNAs of SSTR subtypes (SSTR) 1, 2, 3, and 5, dopamine receptor (D2R), and ERα were measured by real-time quantitative RT-PCR in 59 NFomas and 50 functioning adenomas; the latter included 30 GH-secreting adenomas (GHomas) and 20 prolactinomas (PRLomas). NFomas expressed higher levels of SSTR3 than functioning adenomas but had lower levels of SSTR2, SSTR5 and D2R mRNAs than GHomas. Their ERα levels were higher than those of GHomas. The SSTR subtype mRNA levels in NFomas correlated significantly with each other; there was also a good correlation between the SSTR subtypes and ERα in NFomas. These correlations were largely only observed in younger patients (<50 years). The present study describes the differential expression of SSTR subtypes in the largest number of NFoma patients studied thus far, and further proposes possible involvements of SSTR3 and estrogen in the pathophysiology of NFomas.


Does Resilience Moderate the Relationship Between Stress and Smoking Status?
There is a growing evidence that resilience to stress can promote nonsmoking. However, few studies have undertaken quantitative research to investigate whether resilience, generated by internal and external factors, moderates the impact of stress on the likelihood of smoking. This study aims to help fill this knowledge gap in relation to smokers and ex-smokers, and those people who have never smoked. A large online cross-sectional survey was administered in Australia (2015-2016) to collect data on demographic variables, levels of internal and external resilience, and stress from current and past smokers (n = 400) and those who have never-smoked (n = 921). Logistic regressions were employed to test our hypotheses. Most participants were female (82%) and ranged between 18 and 77 years. Higher levels of reported perceived stress and stress-related variables did significantly predict smoking. The combined impact of internal and external resilience factors predicted never-smoking and lessened the relationship between perceived stress and stress-related variables, and the likelihood of smoking. These results are important because they suggest that the social environment should be developed to augment social support and internal properties such as developing "a strong sense of purpose in life" to encourage people not to commence smoking, rather than focus on smoking cessation.


Laser-assisted removal of aspirated thumbtacks by flexible bronchoscopy.
Background. Aspirated thumbtacks are difficult to extract as the sharp edge of the thumbtack often is well imbedded within bronchial wall and its removal is technically demanding and may cause complications such as bronchial mucosal tear and bronchial wall perforation. These sharp metal objects are commonly removed using rigid bronchoscopy since their removal through flexible bronchoscopy is considered to be dangerous. Objectives. To describe a technique for removal of sharp aspirated metal objects employing laser through flexible bronchoscopy. Methods. We report two patients in whom a new technique for removal of sharp aspirated metal objects utilizing Nd-Yag laser flexible bronchoscopy was used. Results. Successful and uncomplicated removal of the aspirated thumbpack by flexible bronchoscopy under conscious sedation was accomplished in the two patients described. Both patients were discharged within 24 hours. Conclusions. In patients with aspirated thumbtack laser-assisted breakage of the object through flexible bronchoscopy may obviate the need for rigid bronchoscopy or thoracotomy.


The therapeutic use of acetaminophen in patients with liver disease.
Acetaminophen has been used safely and effectively for many years to manage pain and/or fever in patients of all ages. It is commonly recommended as first-line therapy for a variety of patients and conditions, including the elderly, children with viral illnesses, and patients with osteoarthritis, gastrointestinal conditions, bleeding disorders, cardiovascular disease, or renal disease. However, its use is often avoided in patients with chronic liver disease. The perception that acetaminophen should be avoided in such patients arose from awareness of the association between massive acetaminophen overdose and hepatotoxicity, combined with a lack of understanding of the metabolism of acetaminophen in patients with liver disease. There are various theoretical mechanisms of acetaminophen hepatotoxicity in chronic liver disease including: altered metabolism and depleted glutathione stores that would be expected to increase accumulation of the hepatotoxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI). Available studies in patients with chronic liver disease, however, have shown that although the half-life of acetaminophen may be prolonged, cytochrome P-450 activity is not increased and glutathione stores are not depleted to critical levels in those taking recommended doses. Furthermore, acetaminophen has been studied in a variety of liver diseases without evidence of increased risk of hepatotoxicity at currently recommended doses. Therefore, acetaminophen can be used safely in patients with liver disease and is a preferred analgesic/antipyretic because of the absence of the platelet impairment, gastrointestinal toxicity, and nephrotoxicity associated with nonsteroidal antiinflammatory drugs.


The induction of C/EBPβ contributes to vitamin D inhibition of ADAM17 expression and parathyroid hyperplasia in kidney disease.
In secondary hyperparathyroidism (SHPT), enhanced parathyroid levels of transforming growth factor-α (TGFα) increase EGF receptor (EGFR) activation causing parathyroid hyperplasia, high parathyroid hormone (PTH) and also reductions in vitamin D receptor (VDR) that limit vitamin D suppression of SHPT. Since anti-EGFR therapy is not an option in human SHPT, we evaluated ADAM17 as a therapeutic target to suppress parathyroid hyperplasia because ADAM17 is required to release mature TGFα, the most potent EGFR-activating ligand. Computer analysis of the ADAM17 promoter identified TGFα and C/EBPβ as potential regulators of the ADAM17 gene. Their regulation of ADAM17 expression, TGFα/EGFR-driven growth and parathyroid gland (PTG) enlargement were assessed in promoter-reporter assays in A431 cells and corroborated in rat and human SHPT, using erlotinib as anti-EGFR therapy to suppress TGFα signals, active vitamin D to induce C/EBPβ or the combination. While TGFα induced ADAM17-promoter activity by 2.2-fold exacerbating TGFα/EGFR-driven growth, ectopic C/EBPβ expression completely prevented this vicious synergy. Accordingly, in advanced human SHPT, parathyroid ADAM17 levels correlated directly with TGFα and inversely with C/EBPβ. Furthermore, combined erlotinib + calcitriol treatment suppressed TGFα/EGFR-cell growth and PTG enlargement more potently than erlotinib in part through calcitriol induction of C/EBPβ to inhibit ADAM17-promoter activity, mRNA and protein. Importantly, in rat SHPT, the correction of vitamin D deficiency effectively reversed the resistance to paricalcitol induction of C/EBPβ to suppress ADAM17 expression and PTG enlargement, reducing PTH by 50%. In SHPT, correction of vitamin D and calcitriol deficiency induces parathyroid C/EBPβ to efficaciously attenuate the severe ADAM17/TGFα synergy, which drives PTG enlargement and high PTH.


Deterministic forward scatter from surface gravity waves.
Deterministic structures in sound reflected by gravity waves, such as focused arrivals and Doppler shifts, have implications for underwater acoustics and sonar, and the performance of underwater acoustic communications systems. A stationary phase analysis of the Helmholtz-Kirchhoff scattering integral yields the trajectory of focused arrivals and their relationship to the curvature of the surface wave field. Deterministic effects along paths up to 70 water depths long are observed in shallow water measurements of surface-scattered sound at the Martha's Vineyard Coastal Observatory. The arrival time and amplitude of surface-scattered pulses are reconciled with model calculations using measurements of surface waves made with an upward-looking sonar mounted mid-way along the propagation path. The root mean square difference between the modeled and observed pulse arrival amplitude and delay, respectively, normalized by the maximum range of amplitudes and delays, is found to be 0.2 or less for the observation periods analyzed. Cross-correlation coefficients for modeled and observed pulse arrival delays varied from 0.83 to 0.16 depending on surface conditions. Cross-correlation coefficients for normalized pulse energy for the same conditions were small and varied from 0.16 to 0.06. In contrast, the modeled and observed pulse arrival delay and amplitude statistics were in good agreement.


Arginase-negative mutants of Arabidopsis exhibit increased nitric oxide signaling in root development.
Mutation of either arginase structural gene (ARGAH1 or ARGAH2 encoding arginine [Arg] amidohydrolase-1 and -2, respectively) resulted in increased formation of lateral and adventitious roots in Arabidopsis (Arabidopsis thaliana) seedlings and increased nitric oxide (NO) accumulation and efflux, detected by the fluorogenic traps 3-amino,4-aminomethyl-2',7'-difluorofluorescein diacetate and diamino-rhodamine-4M, respectively. Upon seedling exposure to the synthetic auxin naphthaleneacetic acid, NO accumulation was differentially enhanced in argah1-1 and argah2-1 compared with the wild type. In all genotypes, much 3-amino,4-aminomethyl-2',7'-difluorofluorescein diacetate fluorescence originated from mitochondria. The arginases are both localized to the mitochondrial matrix and closely related. However, their expression levels and patterns differ: ARGAH1 encoded the minor activity, and ARGAH1-driven beta-glucuronidase (GUS) was expressed throughout the seedling; the ARGAH2::GUS expression pattern was more localized. Naphthaleneacetic acid increased seedling lateral root numbers (total lateral roots per primary root) in the mutants to twice the number in the wild type, consistent with increased internal NO leading to enhanced auxin signaling in roots. In agreement, argah1-1 and argah2-1 showed increased expression of the auxin-responsive reporter DR5::GUS in root tips, emerging lateral roots, and hypocotyls. We propose that Arg, or an Arg derivative, is a potential NO source and that reduced arginase activity in the mutants results in greater conversion of Arg to NO, thereby potentiating auxin action in roots. This model is supported by supplemental Arg induction of adventitious roots and increased NO accumulation in argah1-1 and argah2-1 versus the wild type.


Chronic exposure to water pollutant trichloroethylene increased epigenetic drift in CD4(+) T cells.
Autoimmune disease and CD4(+) T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4(+) T cells as a possible mechanism of immunotoxicity. Naive and effector/memory CD4(+) T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing. A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4(+) T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets. TCE increased epigenetic drift of specific CpG sites in CD4(+) T cells.


The structure of the hypothetical protein smu.1377c from Streptococcus mutans suggests a role in tRNA modification.
Members of the Sua5_YciO_YrdC protein family are found in both eukaryotes and prokaryotes and possess a conserved alpha/beta twisted open-sheet fold. The Escherichia coli protein YrdC has been shown to be involved in modification of tRNA. The crystal structure of smu.1377c, a hypothetical protein from Streptococcus mutans, has been determined to 2.25 A resolution. From structure analysis and comparison, it is shown that smu.1377c is a member of the Sua5_YciO_YrdC family and that it may play the same role as E. coli YrdC.


Home e-health system integration in the Smart Home through a common media server.
Home e-health systems and services are revealed as one of the most important challenges to promote Quality of Life related to Health in the Information Society. Leading companies have worked on e-health systems although the majority of them are addressed to hospital or primary care settings. The solution detailed in this paper offers a personal health system to be integrated with Smart Home services platform to support home based e-care. Thus, the home e-health system and architecture detailed in this research work is ready to supply a seamless personal care solution both from the biomedical data analysis, service provision, security guarantee and information management s point of view. The solution is ready to be integrated within the Accessible Digital Home, a living lab managed by Universidad Politécnica de Madrid for R&D activities.


Trends in Survival for Pediatric Transplantation.
Progress in pediatric transplantation measured in the context of waitlist and posttransplant survival is well documented but falls short of providing a complete perspective for children and their families. An intent-to-treat analysis, in which we measure survival from listing to death regardless of whether a transplant is received, provides a more comprehensive perspective through which progress can be examined. Univariable and multivariable Cox regression was used to analyze factors impacting intent-to-treat survival in 12 984 children listed for heart transplant, 17 519 children listed for liver transplant, and 16 699 children listed for kidney transplant. The Kaplan-Meier method and log-rank test were used to assess change in waitlist, posttransplant, and intent-to-treat survival. Wait times and transplant rates were compared by using χ2 tests. Intent-to-treat survival steadily improved from 1987 to 2017 in children listed for heart (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.96-0.97), liver (HR 0.95, 95% CI 0.94-0.97), and kidney (HR 0.97, 95% CI 0.95-0.99) transplant. Waitlist and posttransplant survival also improved steadily for all 3 organs. For heart transplant, the percentage of patients transplanted within 1 year significantly increased from 1987 to 2017 (60.8% vs 68.7%); however, no significant increase was observed in liver (68.9% vs 72.5%) or kidney (59.2% vs 62.7%) transplant. Intent-to-treat survival, which is more representative of the patient perspective than individual metrics alone, steadily improved for heart, liver, and kidney transplant over the study period. Further efforts to maximize the donor pool, improve posttransplant outcomes, and optimize patient care while on the waitlist may contribute to future progress.


Time series modelling of global mean temperature for managerial decision-making.
Climate change has important implications for business and economic activity. Effective management of climate change impacts will depend on the availability of accurate and cost-effective forecasts. This paper uses univariate time series techniques to model the properties of a global mean temperature dataset in order to develop a parsimonious forecasting model for managerial decision-making over the short-term horizon. Although the model is estimated on global temperature data, the methodology could also be applied to temperature data at more localised levels. The statistical techniques include seasonal and non-seasonal unit root testing with and without structural breaks, as well as ARIMA and GARCH modelling. A forecasting evaluation shows that the chosen model performs well against rival models. The estimation results confirm the findings of a number of previous studies, namely that global mean temperatures increased significantly throughout the 20th century. The use of GARCH modelling also shows the presence of volatility clustering in the temperature data, and a positive association between volatility and global mean temperature.


Factors influencing prostate cancer screening in low-income African Americans in Tennessee.
This study examined demographic and lifestyle factors that influenced decisions to get screened for prostate cancer in low-income African Americans in three urban Tennessee cities. It also examined obstacles to getting screened. As part of the Meharry Community Networks Program (CNP) needs assessment, a 123-item community survey was administered to assess demographic characteristics, health care access and utilization, and screening practices for various cancers in low-income African Americans. For this study, only African American men 45 years and older (n=293) were selected from the Meharry CNP community survey database. Participants from Nashville, those who were older, obese, and who had health insurance were more likely to have been screened (p<.05). Additionally, there were associations between obstacles to screening (such as cost and transportation) and geographic region (p<.05). Educational interventions aimed at improving prostate cancer knowledge and screening rates should incorporate information about obstacles to and predictors of screening.


Mechanically robust hybrid hydrogels of photo-crosslinkable gelatin and laminin-mimetic peptide amphiphiles for neural induction.
Self-assembling bio-instructive materials that can provide a biomimetic tissue microenvironment with the capability to regulate cellular behaviors represent an attractive platform in regenerative medicine. Herein, we develop a hybrid neuro-instructive hydrogel that combines the properties of a photo-crosslinkable gelatin methacrylate (GelMA) and self-assembling peptide amphiphiles (PAs) bearing a laminin-derived neuro-inductive epitope (PA-GSR). Electrostatic interaction and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hybrid hydrogels with tunable stiffness. Spectroscopic, microscopic and theoretical techniques show that the cationic PA-GSR(+) electrostatically co-assembles with the negatively charged GelMA to create weak hydrogels with hierarchically ordered microstructures, which were further photo-crosslinked to create mechanically robust hydrogels. Dynamic oscillatory rheology and micromechanical testing show that photo-crosslinking of the co-assembled GelMA and PA-GSR(+) hydrogel results in robust hydrogels displaying improved stiffness. Gene expression analysis was used to show that GelMA/PA-GSR(+) hydrogels can induce human mesenchymal stem cells (hMSCs) into neural-lineage cells and supports neural-lineage specification of neuroblast-like cells (SH-SY5Y) in a growth-factor-free manner. Also, metabolomics analysis suggests that the hydrogel alters the metabolite profiles in the cells by affecting multiple molecular pathways. This work highlights a new approach for the design of PA-based hybrid hydrogels with robust mechanical properties and biological functionalities for nerve tissue regeneration.


Problems of video-based pain detection in patients with dementia: a road map to an interdisciplinary solution.
Given the unreliable self-report in patients with dementia, pain assessment should also rely on the observation of pain behaviors, such as facial expressions. Ideal observers should be well trained and should observe the patient continuously in order to pick up any pain-indicative behavior; which are requisitions beyond realistic possibilities of pain care. Therefore, the need for video-based pain detection systems has been repeatedly voiced. Such systems would allow for constant monitoring of pain behaviors and thereby allow for a timely adjustment of pain management in these fragile patients, who are often undertreated for pain. In this road map paper we describe an interdisciplinary approach to develop such a video-based pain detection system. The development starts with the selection of appropriate video material of people in pain as well as the development of technical methods to capture their faces. Furthermore, single facial motions are automatically extracted according to an international coding system. Computer algorithms are trained to detect the combination and timing of those motions, which are pain-indicative. We hope to encourage colleagues to join forces and to inform end-users about an imminent solution of a pressing pain-care problem. For the near future, implementation of such systems can be foreseen to monitor immobile patients in intensive and postoperative care situations.


Neural regulation of the formation of skeletal muscle phosphorylase kinase holoenzyme in adult and developing rat muscle.
Neural influences on the co-ordination of expression of the multiple subunits of skeletal muscle phosphorylase kinase and their assembly to form the holoenzyme complex, alpha4beta4gamma4delta4, have been examined during denervation and re-innervation of adult skeletal muscle and during neonatal muscle development. Denervation of the tibialis anterior and extensor digitorum longus muscles of the rat hindlimb was associated with a rapid decline in the mRNA for the gamma subunit, and an abrupt decrease in gamma-subunit protein. The levels of the alpha- and beta-subunit proteins in the denervated muscles also declined rapidly, their time course of reduction being similar to that for the gamma-subunit protein, but they did not decrease to the same extent. In contrast with the rapid decline in gamma-subunit mRNA upon denervation, alpha- and beta-subunit mRNAs stayed at control innervated levels for approx. 8-10 days, but then decreased rapidly. Their decline coincided very closely with the onset of re-innervation. Re-innervation of the denervated muscles, which occurs rapidly and uniformly after the sciatic nerve crush injury, produced an eventual slow and prolonged recovery of the mRNA for all three subunits and parallel increases in each of the subunit proteins. A similar co-ordinated increase of both subunit mRNA and subunit proteins of the phosphorylase kinase holoenzyme was observed during neonatal muscle development, during the period when the muscles were attaining their adult pattern of motor activity. The phosphorylase kinase holoenzyme remains in a non-activated form during all of these physiological changes, as is compatible with the presence of the full complement of the regulatory subunits. These data are consistent with a model whereby the transcriptional and translational expression of phosphorylase kinase gamma subunit occurs only with concomitant expression of the alpha and beta subunits. This would ensure that free and unregulated, activated gamma subunit alone, which would give rise to unregulated glycogenolysis, is not produced. The data also suggest that control of phosphorylase kinase subunit expression and the formation of the holoenzyme in skeletal muscle is provided by the motor nerve, probably through imposed levels or patterns of muscle activity.


Data quality of animal health records on Swiss dairy farms.
High-quality data are essential for veterinary surveillance systems, and their quality can be affected by the source and the method of collection. Data recorded on farms could provide detailed information about the health of a population of animals, but the accuracy of the data recorded by farmers is uncertain. The aims of this study were to evaluate the quality of the data on animal health recorded on 97 Swiss dairy farms, to compare the quality of the data obtained by different recording systems, and to obtain baseline data on the health of the animals on the 97 farms. Data on animal health were collected from the farms for a year. Their quality was evaluated by assessing the completeness and accuracy of the recorded information, and by comparing farmers' and veterinarians' records. The quality of the data provided by the farmers was satisfactory, although electronic recording systems made it easier to trace the animals treated. The farmers tended to record more health-related events than the veterinarians, although this varied with the event considered, and some events were recorded only by the veterinarians. The farmers' attitude towards data collection was positive. Factors such as motivation, feedback, training, and simplicity and standardisation of data collection were important because they influenced the quality of the data.


Gene regulatory network interactions in sea urchin endomesoderm induction.
A major goal of contemporary studies of embryonic development is to understand large sets of regulatory changes that accompany the phenomenon of embryonic induction. The highly resolved sea urchin pregastrular endomesoderm-gene regulatory network (EM-GRN) provides a unique framework to study the global regulatory interactions underlying endomesoderm induction. Vegetal micromeres of the sea urchin embryo constitute a classic endomesoderm signaling center, whose potential to induce archenteron formation from presumptive ectoderm was demonstrated almost a century ago. In this work, we ectopically activate the primary mesenchyme cell-GRN (PMC-GRN) that operates in micromere progeny by misexpressing the micromere determinant Pmar1 and identify the responding EM-GRN that is induced in animal blastomeres. Using localized loss-of -function analyses in conjunction with expression of endo16, the molecular definition of micromere-dependent endomesoderm specification, we show that the TGFbeta cytokine, ActivinB, is an essential component of this induction in blastomeres that emit this signal, as well as in cells that respond to it. We report that normal pregastrular endomesoderm specification requires activation of the Pmar1-inducible subset of the EM-GRN by the same cytokine, strongly suggesting that early micromere-mediated endomesoderm specification, which regulates timely gastrulation in the sea urchin embryo, is also ActivinB dependent. This study unexpectedly uncovers the existence of an additional uncharacterized micromere signal to endomesoderm progenitors, significantly revising existing models. In one of the first network-level characterizations of an intercellular inductive phenomenon, we describe an important in vivo model of the requirement of ActivinB signaling in the earliest steps of embryonic endomesoderm progenitor specification.


The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4.
BRAF mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. BRAF mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. NRAS mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.


Cationic polymer brush-modified cellulose nanocrystals for high-affinity virus binding.
Surfaces capable of high-affinity binding of biomolecules are required in several biotechnological applications, such as purification, transfection, and sensing. Therein, the rod-shaped, colloidal cellulose nanocrystals (CNCs) are appealing due to their large surface area available for functionalization. In order to exploit electrostatic binding, their intrinsically anionic surfaces have to be cationized as biological supramolecules are predominantly anionic. Here we present a facile way to prepare cationic CNCs by surface-initiated atom-transfer radical polymerization of poly(N,N-dimethylaminoethyl methacrylate) and subsequent quaternization of the polymer pendant amino groups. The cationic polymer brush-modified CNCs maintained excellent dispersibility and colloidal stability in water and showed a ζ-potential of +38 mV. Dynamic light scattering and electron microscopy showed that the modified CNCs electrostatically bind cowpea chlorotic mottle virus and norovirus-like particles with high affinity. Addition of only a few weight percent of the modified CNCs in water dispersions sufficed to fully bind the virus capsids to form micrometer-sized assemblies. This enabled the concentration and extraction of the virus particles from solution by low-speed centrifugation. These results show the feasibility of the modified CNCs in virus binding and concentrating, and pave the way for their use as transduction enhancers for viral delivery applications.


[Diverticulosis of the large intestine].
Under observation were 47 patients with colonic diverticula. The clinical classification of diverticulosis of the colon is suggested. The principal method of treatment in patients with uncomplicated forms of the diverticulosis should be conservative. In profuse hemorrhage and intestinal obstruction as well as in perforation of the diverticulum, that would not respond to conservative therapy, surgery is indicated.


Factors Influencing Drug Use Information Received at Primary Healthcare Centre Pharmacies in Ghana.
Health literacy addresses environmental, political, and social factors that determine health. Drug dispensers play a major role in educating patients on drug use to increase effective and efficient drug utilisation, thereby promoting positive healthcare outcomes. From the patients' perspective, this study examined the communication quality between patients and drug dispensers at primary healthcare centres in the Cape Coast Metropolis of Ghana. We conveniently surveyed 269 patients seeking health care at primary healthcare facilities using a researcher-constructed 13-item instrument. In SPSS version 21 software, we analysed the data using percentages, chi-square analysis, and logistic regression. Almost half of the participants (n = 132) reported low health literacy, with 81% (n = 218) reporting that drug side effects were not discussed with them at the pharmacies. The findings further indicated that health literacy and educational level predicted general communication quality between participants and drug dispensers; participants with secondary education were about 3 times more likely to report not being told of the side effects of prescribed drugs as compared with those who had completed only basic education. There is still a high level of low health literacy among patients seeking healthcare at primary healthcare centres and a very high percentage of patients did not receive any education on side effects of dispensed drugs. Drug use directives from dispensers at primary healthcare facilities can make a difference between any 2 patients.


Total Synthesis Establishes the Biosynthetic Pathway to the Naphterpin and Marinone Natural Products.
The naphterpins and marinones are naphthoquinone meroterpenoids with an unusual aromatic oxidation pattern that is biosynthesized from 1,3,6,8-tetrahydroxynaphthalene (THN). We propose that cryptic halogenation of THN derivatives by vanadium-dependent chloroperoxidase (VCPO) enzymes is key to this biosynthetic pathway, despite the absence of chlorine in these natural products. This speculation inspired a total synthesis to mimic the naphterpin/marinone biosynthetic pathway. In validation of this biogenetic hypothesis, two VCPOs were discovered that interconvert several of the proposed biosynthetic intermediates.


Molecular Characterization of Indigenous Rhizobia from Kenyan Soils Nodulating with Common Beans.
Kenya is the seventh most prominent producer of common beans globally and the second leading producer in East Africa. However, the annual national productivity is low due to insufficient quantities of vital nutrients and nitrogen in the soils. Rhizobia are symbiotic bacteria that fix nitrogen through their interaction with leguminous plants. Nevertheless, inoculating beans with commercial rhizobia inoculants results in sparse nodulation and low nitrogen supply to the host plants because these strains are poorly adapted to the local soils. Several studies describe native rhizobia with much better symbiotic capabilities than commercial strains, but only a few have conducted field studies. This study aimed to test the competence of new rhizobia strains that we isolated from Western Kenya soils and for which the symbiotic efficiency was successfully determined in greenhouse experiments. Furthermore, we present and analyze the whole-genome sequence for a promising candidate for agricultural application, which has high nitrogen fixation features and promotes common bean yields in field studies. Plants inoculated with the rhizobial isolate S3 or with a consortium of local isolates (COMB), including S3, produced a significantly higher number of seeds and seed dry weight when compared to uninoculated control plants at two study sites. The performance of plants inoculated with commercial isolate CIAT899 was not significantly different from uninoculated plants (p > 0.05), indicating tight competition from native rhizobia for nodule occupancy. Pangenome analysis and the overall genome-related indices showed that S3 is a member of R. phaseoli. However, synteny analysis revealed significant differences in the gene order, orientation, and copy numbers between S3 and the reference R. phaseoli. Isolate S3 is phylogenomically similar to R. phaseoli. However, it has undergone significant genome rearrangements (global mutagenesis) to adapt to harsh conditions in Kenyan soils. Its high nitrogen fixation ability shows optimal adaptation to Kenyan soils, and the strain can potentially replace nitrogenous fertilizer application. We recommend that extensive fieldwork in other parts of the country over a period of five years be performed on S3 to check on how the yield changes with varying whether conditions.


Professional development of sport psychology practitioners: From systematic review to a model of development.
A clear model of professional development (PD) has the potential to enhance educational and training programs and promote effective, competent, and ethical practice. Scholars have explored facets of the PD of sport psychology practitioners (SPPs) using theoretical frameworks borrowed from counseling psychology. Yet, given the emergence of a sport-specific body of work on this topic, it appears timely to take stock of existing context-specific knowledge. In the present study, we aimed to systematically review the extant literature focused on SPP's PD to identify specific characteristics and organize this knowledge in an accessible and structured manner in the form of a process model of PD. Following the PRISMA guidelines, we identified 1147 research records in the databases SportDiscuss, PsychArticles, PsychInfo, ProQuest, and PubMed. We subsequently screened and assessed the records for eligibility (i.e., empirical studies published in English that focus on developmental characteristics of SPPs, including a clear developmental stage) reducing the sample of articles that fitted our inclusion criteria to 34 qualitative manuscripts. Finally, we critically explored these manuscripts by engaging in a reflexive thematic analysis and created four developmental phases (i.e., introduction, exploration, solidification, and fulfillment). SPPs' transition through these phases is seemingly facilitated by four processes (i.e., reflection, supervision, connections and networking with peers, and learning by doing), which also support the completion of the tasks associated with nine developmental elements (i.e., purpose, confidence and anxiety, focus, awareness, adaptability, independence, philosophy/congruence, professional identity, and the individual). We present the interaction of these developmental phases, elements, and processes in the form of a sport psychology-specific process model of PD. We discuss the implications of this model and its potential contribution to future research, supervision, and training programs. Yet, we also acknowledge how a focus on Anglophone and Western cultural contexts and a lack of methodological transparency are limitations of the extant literature.


An Assessment of Domestic Financing for Reproductive, Maternal, Neonatal and Child Health in Sub-Saharan Africa: Potential Gains and Fiscal Space.
Reproductive, maternal, neonatal and child health (RMNCH) remains an important public health objective. In sub-Saharan Africa (SSA), inadequate financial commitment continues to pose a major challenge to improving RMNCH outcomes. Understanding financing gains and potential fiscal space for RMNCH can therefore not be overemphasized. This study sought to analyse the potential gains from increased domestic financing as a source for improving RMNCH outcomes in SSA. We also assessed, in addition to the potential gains, the potential fiscal space available for financing RMNCH in SSA. Our study used panel econometric techniques to estimate gains from increased health financing in terms of RMNCH. We also reviewed tax system performance as well as debt sustainability to identify fiscal space potentials across countries. We found significant gains from both domestic and external financing. The estimated elasticities suggest that the gains from domestic public financing were much stronger. The fiscal space options identified include tax revenue performance improvements, improved public financial management, and borrowing, at least in the short to medium term. The results show that fiscal space from improved tax systems ranged from US$34.6 per capita in Uganda to US$310.6 per capita in Nigeria. This result reinforces calls for increased domestic financing for health through innovations in domestic resource mobilization. Improving the performance of tax systems will be a step in the right direction, with possible long-term gains to the health sector.


Prions hijack tunnelling nanotubes for intercellular spread.
In variant Creutzfeldt-Jakob disease, prions (PrP(Sc)) enter the body with contaminated foodstuffs and can spread from the intestinal entry site to the central nervous system (CNS) by intercellular transfer from the lymphoid system to the peripheral nervous system (PNS). Although several means and different cell types have been proposed to have a role, the mechanism of cell-to-cell spreading remains elusive. Tunnelling nanotubes (TNTs) have been identified between cells, both in vitro and in vivo, and may represent a conserved means of cell-to-cell communication. Here we show that TNTs allow transfer of exogenous and endogenous PrP(Sc) between infected and naive neuronal CAD cells. Significantly, transfer of endogenous PrP(Sc) aggregates was detected exclusively when cells chronically infected with the 139A mouse prion strain were connected to mouse CAD cells by means of TNTs, identifying TNTs as an efficient route for PrP(Sc) spreading in neuronal cells. In addition, we detected the transfer of labelled PrP(Sc) from bone marrow-derived dendritic cells to primary neurons connected through TNTs. Because dendritic cells can interact with peripheral neurons in lymphoid organs, TNT-mediated intercellular transfer would allow neurons to transport prions retrogradely to the CNS. We therefore propose that TNTs are involved in the spreading of PrP(Sc) within neurons in the CNS and from the peripheral site of entry to the PNS by neuroimmune interactions with dendritic cells.


Facial Fenestration and Dehiscence Defects Associated With Immediate Implant Placement Without Flap Elevation in Anterior Maxillary Ridge: A Preliminary Cone Beam Computed Tomography Study.
To examine cone beam computed tomography (CBCT) anatomical findings, such as the concavity of the ridge and angulation of the tooth and alveolar ridge, either facial or palatal, in order to assess the potential clinical risks of performing flapless implant surgery. CBCT images that met the inclusion criteria were examined. All images in maxillary anterior areas (canine to canine), facial bone thickness at 3 and 5 mm from the cementoenamel junction (CEJ), angulation of the tooth and alveolar ridge (Angle T: the angulation between the long axis of the tooth and the palatal plane; Angle D: the angulation between the long axis of the tooth and the midline of the ridge), the deepest point of facial concavity, the distance from the deepest point of facial concavity to the apex of the tooth and alveolar bone crest, nasopalatine canal, dehiscence, and fenestrations were measured and statistically analyzed. In total, 21 patients (12 women and 9 men) with a mean age of 55.9 years who met the inclusion criteria were included in the analysis. Data from 21 patients, 6 image sections per patient (total of 126 CBCT images) were analyzed. The mean value of facial bone thickness was 0.99 mm and 0.60 mm at 3 and 5 mm from CEJ, respectively. The distance from the deepest point of facial concavity to the apex of the tooth and alveolar bone crest was 2.79 and 11.29 mm, respectively. In canine areas, the mean values of facial bone thickness were larger at 3 mm but thinner at 5 mm. Also, canines were found to have a larger Angle D and a higher incidence of fenestration and dehiscence. Based on the findings, fenestration and a larger Angle D were associated with thinner facial bone thickness at 5 mm, and the tooth types also had an impact. Hence, for immediate implant surgery without flap elevation, besides anatomical structures, both angulation of the tooth and the alveolar ridge also need to be assessed.


Application of the theory of steady-state flux control to mitochondrial beta-oxidation.
The theory of steady-state flux control was applied to characterize the regulation of beta-oxidation flux in uncoupled rat liver mitochondria oxidizing palmitoylcarnitine in the presence of rotenone, malonate and the beta-hydroxybutyrate/acetoacetate redox buffer. By titrations with inhibitors such as antimycin, myxothiazol, azide and 4-pentenoic acid, the flux control coefficients of the b-c1 complex, cytochrome c oxidase and thiolase, were determined experimentally. The flux control coefficients of carnitine palmitoyltransferase II, ETF:CoQ oxidoreductase and beta-hydroxybutyrate dehydrogenase were determined from elasticity coefficients obtained by measuring the flux dependencies of acyl-CoA and acetyl-CoA+CoASH concentrations, the electron transfer flavoprotein redox state, the CoQ redox state and the NAD redox state. It was found that at low flux rates the flux control was distributed mainly between acyl-CoA dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase (Ci = 0.89). At maximum flux rates, carnitine palmitoyltransferase II (Ci = 0.35) and thiolase (Ci = 0.13) contribute additionally to the flux control. Thus, the phenomena of regulation of mitochondrial beta-oxidation can be described as multistep control.


Molecular Structure of Pyrazinamide: A Critical Assessment of Modern Gas Electron Diffraction Data from Three Laboratories.
Accuracy and precision of molecular parameters determined by modern gas electron diffraction have been investigated. Diffraction patterns of gaseous pyrazinamide have been measured independently in three laboratories, in Bielefeld (Germany), Ivanovo (Russia), and Moscow (Russia). All data sets have been analyzed in equal manner using a highly controlled background elimination procedure and flexible restraints in molecular structure refinement. In detailed examination and comparison of the obtained results we have determined the average experimental precision of 0.004 Å for bond lengths and 0.2° for angles. The corresponding average deviations of the refined parameters from the ae-CCSD(T)/cc-pwCVTZ theoretical values were 0.003 Å and 0.2°. The average precision for refined amplitudes of interatomic vibrations was determined to be 0.005 Å. It is recommended to take into account these values in calculations of total errors for refined parameters of other molecules with comparable complexity.


Health care system reforms in developing countries.
This article proposes a critical but non-systematic review of recent health care system reforms in developing countries. The literature reports mixed results as to whether reforms improve the financial protection of the poor or not. We discuss the reasons for these differences by comparing three representative countries: Mexico, Vietnam, and China. First, the design of the health care system reform, as well as the summary of its evaluation, is briefly described for each country. Then, the discussion is developed along two lines: policy design and evaluation methodology. The review suggests that i) background differences, such as social development, poverty level, and population health should be considered when taking other countries as a model; ii) although demand-side reforms can be improved, more attention should be paid to supply-side reforms; and iii) the findings of empirical evaluation might be biased due to the evaluation design, the choice of outcome, data quality, and evaluation methodology, which should be borne in mind when designing health care system reforms.


Quantum simulation of antiferromagnetic spin chains in an optical lattice.
Understanding exotic forms of magnetism in quantum mechanical systems is a central goal of modern condensed matter physics, with implications for systems ranging from high-temperature superconductors to spintronic devices. Simulating magnetic materials in the vicinity of a quantum phase transition is computationally intractable on classical computers, owing to the extreme complexity arising from quantum entanglement between the constituent magnetic spins. Here we use a degenerate Bose gas of rubidium atoms confined in an optical lattice to simulate a chain of interacting quantum Ising spins as they undergo a phase transition. Strong spin interactions are achieved through a site-occupation to pseudo-spin mapping. As we vary a magnetic field, quantum fluctuations drive a phase transition from a paramagnetic phase into an antiferromagnetic phase. In the paramagnetic phase, the interaction between the spins is overwhelmed by the applied field, which aligns the spins. In the antiferromagnetic phase, the interaction dominates and produces staggered magnetic ordering. Magnetic domain formation is observed through both in situ site-resolved imaging and noise correlation measurements. By demonstrating a route to quantum magnetism in an optical lattice, this work should facilitate further investigations of magnetic models using ultracold atoms, thereby improving our understanding of real magnetic materials.


[Protective effect of a commercial vaccine, poludan and their combinations in an experimental herpes infection].
The antiviral action of herpes vaccine and poludan, an interferon-inducing agent, has been studied in experimental herpes infection, and the synergic effect of these preparations has been obtained. The best result (survival rate equal to 100% after the intraperitoneal inoculation of herpes simplex virus and 85.7% after its intracerebral inoculation) has been registered after the multiple vaccination of experimental animals and the injection of poludan 1 day before the challenge of the animals with the virus. The protective effect of the synergic action of the preparations under study coincides with the period of the maximum content of antibodies in the blood sera of the animals.


Perceptual learning reduces interneuronal correlations in macaque visual cortex.
Responses of neurons in early visual cortex change little with training and appear insufficient to account for perceptual learning. Behavioral performance, however, relies on population activity, and the accuracy of a population code is constrained by correlated noise among neurons. We tested whether training changes interneuronal correlations in the dorsal medial superior temporal area, which is involved in multisensory heading perception. Pairs of single units were recorded simultaneously in two groups of subjects: animals trained extensively in a heading discrimination task, and "naive" animals that performed a passive fixation task. Correlated noise was significantly weaker in trained versus naive animals, which might be expected to improve coding efficiency. However, we show that the observed uniform reduction in noise correlations leads to little change in population coding efficiency when all neurons are decoded. Thus, global changes in correlated noise among sensory neurons may be insufficient to account for perceptual learning.


Assessment of the carpal tunnel outcome instrument in patients with nerve-compression symptoms.
The outcome movement in medicine has encouraged the development of patient-answered questionnaires as measures of well-being. A disease-specific questionnaire for carpal tunnel syndrome (CTS) was introduced by Levine et al. in 1993. We evaluated this questionnaire in 156 consecutive new patients presenting with pain, numbness, or tingling of the upper extremity. Of these, 114 correctly filled out the carpal tunnel outcome instrument. In addition, these patients completed the self-administered hand diagram developed by Katz and Stirrat for the diagnosis of CTS. The 114 patients were classified according to their hand diagram as classic or probable CTS (n = 47), possible CTS (n = 31), and unlikely CTS (n = 36). The mean symptom severity score in patients classified as classic or probable CTS was significantly higher than the mean score in patients classified as possible or unlikely CTS (p < .01). The mean scores of items regarding sensory symptoms were significantly higher in patients with classic or probable CTS compared to patients with possible or unlikely CTS (p < .0001). The scores were similar for CTS and non-CTS patients on the functional status subscale.


Individual Physiological Adaptations Enable Selected Bacterial Taxa To Prevail during Long-Term Incubations.
Enclosure experiments are frequently used to investigate the impact of changing environmental conditions on microbial assemblages. Yet, how the incubation itself challenges complex bacterial communities is thus far unknown. In this study, metaproteomic profiling, 16S rRNA gene analyses, and cell counts were combined to evaluate bacterial communities derived from marine, mesohaline, and oligohaline conditions after long-term batch incubations. Early in the experiment, the three bacterial communities were highly diverse and differed significantly in their compositions. Manipulation of the enclosures with terrigenous dissolved organic carbon resulted in notable differences compared to the control enclosures at this early phase of the experiment. However, after 55 days, bacterial communities in the manipulated and the control enclosures under marine and mesohaline conditions were all dominated by gammaproteobacterium Spongiibacter In the oligohaline enclosures, actinobacterial cluster I of the hgc group (hgc-I) remained abundant in the late phase of the incubation. Metaproteome analyses suggested that the ability to use outer membrane-based internal energy stores, in addition to the previously described grazing resistance, may enable the gammaproteobacterium Spongiibacter to prevail in long-time incubations. Under oligohaline conditions, the utilization of external recalcitrant carbon appeared to be more important (hgc-I). Enclosure experiments with complex natural microbial communities are important tools to investigate the effects of manipulations. However, species-specific properties, such as individual carbon storage strategies, can cause manipulation-independent effects and need to be considered when interpreting results from enclosures.IMPORTANCE In microbial ecology, enclosure studies are often used to investigate the effect of single environmental factors on complex bacterial communities. However, in addition to the manipulation, unintended effects ("bottle effect") may occur due to the enclosure itself. In this study, we analyzed the bacterial communities that originated from three different salinities of the Baltic Sea, comparing their compositions and physiological activities both at the early stage and after 55 days of incubation. Our results suggested that internal carbon storage strategies impact the success of certain bacterial species, independent of the experimental manipulation. Thus, while enclosure experiments remain valid tools in environmental research, microbial community composition shifts must be critically followed. This investigation of the metaproteome during long-term batch enclosures expanded our current understanding of the so-called "bottle effect," which is well known to occur during enclosure experiments.


Assessing Risks to Wildlife from Free-Roaming Hybrid Cats: The Proposed Introduction of Pet Savannah Cats to Australia as a Case Study.
Hybrid cats-created by crossing different species within the family Felidae-are popular pets, but they could potentially threaten native species if they escape and establish free-roaming populations. To forestall this possibility, the Australian government imposed a specific ban on importation of the savannah cat, a hybrid created by crossing the domestic cat Felis catus and serval Leptailurus serval, in 2008. We develop a decision-framework that identifies those species of non-volant native mammals in Australia that would likely have been susceptible to predation by savannah cats if importation and establishment had occurred. We assumed that savannah cats would hunt ecologically similar prey to those that are depredated by both the domestic cat and the serval, and categorised native mammals as having different levels of susceptibility to predation by savannah cats based on their size, habitat range, and behaviour. Using this framework, we assessed savannah cats as likely to add at least 28 extant native mammal species to the 168 that are known already to be susceptible to predation by the domestic cat, posing a risk to 91% of Australia's extant non-volant terrestrial mammal species (n = 216) and to 93% of threatened mammal species. The framework could be generalised to assess risks from any other hybrid taxa.


[Avoidable mortality. Changes in the new century?].
To analyze time trends and the geographical distribution of avoidable mortality in the autonomous community of Valencia and its health departments by sex in the periods 1990-1994, 1995-1999, and 2000-2004. Twenty-one causes of avoidable mortality were analyzed. The deaths analyzed corresponded to residents in the autonomous community of Valencia between 1990 and 2004. Age-standardized mortality rates were calculated using the direct method. To study time trends in the geographical area of interest for each period and sex, comparative mortality ratios were calculated. To analyze geographical distribution, standardized mortality rates were calculated by the indirect method. The total number of avoidable deaths was 38,061 (7.1% of overall deaths). Men accounted for 76.2% and women for 23.8%. By groups, 82.4% were preventable and 17.6% were treatable. Preventable deaths represented 86.5% of deaths in men and 69.4% of those in women. Avoidable mortality in Valencia significantly decreased in both sexes, this decrease being more marked in the group of treatable deaths and in men. Mortality from lung cancer in women significantly increased. Between 2000 and 2004, none of the health departments showed a significant excess of treatable mortality. In the autonomous community of Valencia, there was a greater decrease in avoidable mortality than in general mortality. The increase in lung cancer in women was notable.


Targeted nanoparticles for enhanced X-ray radiation killing of multidrug-resistant bacteria.
This paper describes a nanoparticle enhanced X-ray irradiation based strategy that can be used to kill multidrug resistant (MDR) bacteria. In the proof-of-concept experiment using MDR Pseudomonas aeruginosa (P. aeruginosa) as an example, polyclonal antibody modified bismuth nanoparticles are introduced into bacterial culture to specifically target P. aeruginosa. After washing off uncombined bismuth nanoparticles, the bacteria are irradiated with X-rays, using a setup that mimics a deeply buried wound in humans. Results show that up to 90% of MDR P. aeruginosa are killed in the presence of 200 μg ml(-1) bismuth nanoparticles, whereas only ∼6% are killed in the absence of bismuth nanoparticles when exposed to 40 kVp X-rays for 10 min. The 200 μg ml(-1) bismuth nanoparticles enhance localized X-ray dose by 35 times higher than the control with no nanoparticles. In addition, no significant harmful effects on human cells (HeLa and MG-63 cells) have been observed with 200 μg ml(-1) bismuth nanoparticles and 10 min 40 kVp X-ray irradiation exposures, rendering the potential for future clinical use. Since X-rays can easily penetrate human tissues, this bactericidal strategy has the potential to be used in effectively killing deeply buried MDR bacteria in vivo.